Cool Videos: Pushing the Limits of Live-Cell Microscopy

If you&rsquo;re not watching recent work in biology, you might have thought that light microscopy hit its limits years ago.&nbsp; After all, it&rsquo;s been around a long time. But to the contrary, microscopic imaging technology just keeps getting better and better. Here you can look with unprecedented clarity at just one of the many dynamic processes going on within a living cell. Specifically, this video shows actin fibers (orange-red), which are key components of the cell&rsquo;s cytoskeleton, slowly pulling clathrin-coated pits (green), which are basket-like structures containing molecular cargo, away from the cell&rsquo;s external membrane and deeper within the cell.

This remarkable live-action view was produced using one of two new forms of extended-resolution, structured illumination microscopy (SIM). SIM is faster than other forms of super-resolution fluorescence microscopy. It&rsquo;s also less damaging to cells, making it the go-to method for live-cell imaging. The downside has been SIM&rsquo;s limited resolution—just twice that of conventional light microscopes. However, Nobel Prize-winner Eric Betzig and postdoc Dong Li of Howard Hughes Medical Institute, Janelia Farms, Ashburn, VA, along with colleagues including Jordan Beach and John Hammer at NIH&rsquo;s National Heart, Lung, and Blood Institute, recently came up with two different solutions to enhance SIM&rsquo;s spatial resolution.

Betzig was one of three scientists awarded the 2014 Nobel Prize in Chemistry for the development of another innovative microscopic imaging technology, known as super-resolved fluorescence microscopy. That technology is credited with producing the first super-resolution images of intact cells. (As an interesting aside, Betzig&rsquo;s microscope was first developed at NIH&rsquo;s Eunice Kennedy Shriver National Institute of Child Health and Human Development, at a time when Betzig had been working out of a cottage in rural Michigan!)

Betzig and his colleagues recognized, however, that their Nobel Prize-winning approach had certain limitations when it came to imaging events as they unfold in real-time inside living cells.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.